Peripheral blood lymphocytes from patients with multiple sclerosis (MS) adhere to virus infected cells in significantly greater numbers than lymphocytes from controls. Prostaglandins of the E series (PGE) and dibutyryl cyclic AMP increase control lymphocyte adherence determinations (LAD) to MS levels. Inhibition of PG synthesis by aspirin (ASA) or indomethacin in MS lymphocytes (in vivo or in vitro) decreases LAD to control levels. Lymphocytes from MS patients form less large or "avid" rosettes with sheep erythrocytes (SE) than control lymphocytes. PGE1 reduces formation of avid E-rosettes in controls and ASA (in vivo and in vitro) increases avid E-rosette formation in MS patients. Thus, an inverse relationship exists between LAD and avid E-rosette formation and both functions may be controlled by a prostaglandin-sensitive mechanism. These data suggest that prostaglandin and cyclic nucleotide metabolism and subsequent control of immune reactions may be altered in patients with MS. Since in vitro systems that involve cell surface interactions are models of immunological reactions we will study the mechanisms responsible for altered lymphocyte adherence in MS patients. In particular, we will measure the amount of prostaglandins E2 and F2 alpha, and cyclic nucleotides (cAMP, cGMP), produced in tissue culture by mononuclear cells, non adherent (T) cells, adherent cells (monocytes) and T cell subpopulations, spontaneously and following antigenic stimulation or coculture with virus infected cells. We will attempt to determine whether MS lymphocytes respond to prostaglandins in a manner different from non-MS lymphocytes. We will therefore study the effect of PG on calcium fluxes in these cells and the effect of calcium fluxes on LAD. Analysis will include studies of the effects of cyclic nucleotides, compounds which alter cellular cyclic nucleotide concentrations, compounds which influence PG synthesis, and another compound thought to regulate immune responses (interferon) on LAD, E-rosette formation (active spontaneous total and avid) and on spontaneous mononuclear cell mediated cytotoxicity (to virus infected cells). LAD may be a prelude to cytotoxicity. Ultrastructural studies of mononuclear cell - HEp-2 cell interactions will be done.